This program project on Thrombosis, Platelets, and Plasma Proteins has as its broad goal the description of the mechanism(s) by which coagulation and clot lysis are regulated and coupled. This goal includes the application of this information to studies of abnormalities of coagulation and clot lysis in patients with thrombosis. The structure-formation of certain pro-coagulant (Factor V, prothrombin) and fibrinolytic (streptokinase, plasminogen activator, and activated protein C) proteins is being studied. Their relationship with platelets and their role in more complex platelet-plasma systems in which coagulation and/or clot lysis occur, is being defined. This information in turn is being applied to a description of and development of diagnostic approaches to thrombosis. In all these studies, particular emphasis is placed on the role of catalytic surfaces, regulatory surfaces, regulatory proteins, their sub units and reaction products in regulation of coagulation and clot lysis. These goals involve a committment to and the collaboration of at least 20 independent investigators specialyzing in the following techniques and fields: protein amino acid sequencing, crystallography, nuclear magnetic resonance, structure-formation of coagulation and of fibrinolytic plasma proteins, platelet metabolism and cytoskeleton, platelet ultra-structure, pathophysiology of shock, and clinical coagulation and thrombosis.